Literature review and proposal of best practice for ophthalmologists: monitoring of patients following intravitreal brolucizumab therapy

Abstract

Brolucizumab is a novel humanised, single-chain, variable fragment inhibitor of Vascular Endothelial Growth Factor-A for the treatment of neurovascular age-related macular degeneration. Brolucizumab gained US Food and Drug Administration and European Medicines Agency approval following the Phase III HAWK (NCT02307682) and HARRIER (NCT02434328) trials which compared brolucizumab with aflibercept, presenting a tolerable safety and favourable efficacy profile. The mean change (least squares [LS] mean ± standard error) in best-corrected visual acuity letters from baseline to week 96 in the HAWK trial was 5.9 ± 0.78 for brolucizumab (6 mg) versus 5.3 ± 0.78 for aflibercept, and in the HARRIER trial, 6.1 ± 0.73 (6 mg) for brolucizumab (6 mg) and 6.6 ± 0.73 for aflibercept. Within both trials, greater reductions were noted in the central subfield thickness from baseline to week 96 in the brolucizumab (6 mg) groups versus the aflibercept group. Subsequent post-marketing reports detailed intraocular inflammation (IOI) after brolucizumab treatment and in response an independent safety review committee conducted a post hoc data review. While comparable, the rate of brolucizumab-associated IOI was higher in the post hoc analysis than the trials (4.6% and 4.4%, respectively). Findings from trials and real-world data indicate there may be pre-defining risk factors that predispose patients to IOI following brolucizumab treatment. With a thorough understanding of IOI classification and best practice management, ophthalmologists can use brolucizumab confidently and, should a case arise, they should act quickly to prevent vision loss. Herein, we provide information and guidance to support clinical decision-making related to brolucizumab use.

Keywords: Anti-VEGF; Brolucizumab; Intraocular inflammation; Retinal occlusion; Retinal vasculitis; Safety findings.

Fig. 1

Brolucizumab treatment pathway. Abbreviations: BCVA, best-corrected visual acuity, H&S, history and symptoms, FFA, fundus fluorescein angiography, IOI, intraocular inflammation OCT, optical coherence tomography, SLB, slit lamp biomicroscopy, VA, visual acuity